Patent GB-517272-A (GB)
Title: The preparation of new therapeutically useful heterocyclic compounds
IPC: C07D277/56
Filed: 1938-06-03
Abstract: 517,272. Sulphonamido derivatives of thiazoles. MAY & BAKER, Ltd., NEWBERY, G., and VIAUD, P. June 3, 1938, Nos. 16719 and 26963. [Class 2 (iii)] 2-(p-Aminobenzene-sulphonamido) derivatives of thiazole and benzothiazole and their substituted derivatives of the general formula p-NH2-C6H4SO2NRR<1> where R is hydrogen or alkyl or aralkyl and R<1> is a thiazole or benzthiazole residue are prepared by condensing benzene sulphonyl halides with a 2-amino thiazole or benzthiazole or by condensing a benzene sulphonamide with a 2-halogen thiazole or benzthiazole in which the benzene sulphonyl compound is substituted in the para position by an acylamino group, a nitro group or by an azo group linked to an organic radical or a halogen, followed by hydrolysis in the first case, reduction in the second and third cases and treatment with ammonia in the fourth case. In place of the benzene sulphonyl halides above the corresponding anhydrides may be used. One or more of'the hydrogen atoms in the thiazole or the benzthiazole residue may be replaced by the group nitro-amino, acylamino, alkyl, aryl, alkoxyl, hydroxy-alkyl or carbalkoxy. Derivatives in which R in the above formula is alkyl are obtained by the action of alkyl sulphates on the alkaline solutions of the amino derivatives obtained above. In examples (1) 2-amino-thiazole is reacted in pyridine solution with p-acetylamino benzene-sulphonyl chloride and the product hydrolyzed to give 2 (p-aminobenzenesulphamidothiazole). (2) 2- amino-4-methylthiazole hydrochloride is reacted in pyridine solution with p-bromobenzenesulphonyl chloride and the product heated with ammonia in the presence of cuprous chloride to give 2 (-p-aminobenzenesulphamido)-4-methylthiazole. (3) Azobenzenep-sulphonyl chloride is reacted in pyridine solution with 2-amino-4-methyl thiazole hydrochloride, and the product reduced with Raney nickel catalyst in alcohol solution to 2-(paminobenzene-sulphonamido)-4-methylthiazole. (4) 2 amino-4-methyl thiazole is reacted in pyridine solution with p acetyl-aminobenzene sulphonyl chloride, and the product hydrolyzed with aqueous hydrochloric acid to 2-(p-aminobenzene-sulphonamido)-4-methylthiazole. (5) 2-amino-5-methyl thiazole is reacted in pyridine solution with p-acetylamino-benzenesulphonyl chloride and the product hydrolyzed with 2N sodium hydroxide to give 2-(p-aminobenzenesulphonamido)-5-methyl thiazole. (6) 2-amino- 4:5-dimethylthiazole hydrochloride is reacted in pyridine solution with p-nitro-benzene sulphonic anhydride, and the product hydrolyzed by treatment with a paste of sodium hydroxide and ferrous hydroxide to give 2-(p-aminobenzenesulphonamido)-4:5-dimethylthiazole. (7) 2-amino-4-methyl-5-phenylthiazole is condensed in pyridine solution with p-acetylamino-benzenesulphonyl chloride and the product hydrolyzed with 2N sodium hydroxide' to give 2 (p-aminobenzenesulphonamido) - 4 - methyl - 5. phenylthiazole. (8) 2-amino-4 phenylthiazole is reacted in pyridine solution with p-acetylaminobenzene-sulphonyl chloride and the product hydrolyzed with 2N sodium hydroxide to give 2 (p-aminobenzenesulphonamido)-4 phenylthiazole. (9) 2-amino-4-methyl-5 hydroxyethyl thiazole prepared by condensation of thiourea with 3-chloro-3-aceto-propone-ol-1 is reacted in aqueous solution with p-acetylaminobenzenesulphonyl chloride, and the product is hydrolyzed by boiling with methane sulphonic acid to give 2 (p-aminobenzenesulphonamido) - 4 - methyl - 5 - hydroxyethylthiazole. (10) 2-amino-4-methyl-5-carbethoxythiazole is reacted in pyridine solution with p-acetylaminobenzenesulphonyl chloride. This' is treated with 15 per cent. hydrochloric acid to give 2 (p-aminobenzenesulphonamido)-4-methyl-5-carbethoxythiazole. Saponification with caustic soda yields the corresponding 5-carboxy-compound. (11) p-acetylaminobenzenesulphonamide is heated with an equal weight of 2- bromo-benzthiazole in the presence of dry potassium carbonate and a small amount of copper bronze. Hydrolysis of the product with concentrated hydrochloric acid gives 2 (paminobenzenesulphonamido) benzthiazole. (12) 2-aminobenzthiazole is reacted in pyridine solution. with p-acetylaminobenzenesulphonyl chloride, and the product hydrolysed with caustic soda to give 2(-p-aminobenzenesulphonamido) benzthiazole. (13) 2-amino-6-ethoxybenzthiazole is reacted in pyridine solution with p-acetyl-aminobenzenesulphonyl chloride, and the product hydrolysed by passing hydrochloric gas into its alcoholic solution to give 2(p-aminobenzenesulphonamido)- 6 - ethoxybenthiazole. (14) 2-amino-6-nitrobenzthiazole is reacted in pyridine solution with p-acetylaminobenzenesulphonyl chloride and the product hydrolysed with caustic soda to give 2 (p-aminobenzenesulphohamido)-6-nitrobenzthiazole. (15) 2 - amino - 5 - acetyl - aminobenzthiazole is reacted in pyridine solution with p-acetylaminobenzenesulphonyl chloride and the product hydrolysed with caustic soda to give 2 (p-aminobenzenesulphonamido)-5- aminobenzthiazole. (16) 2-amino-5-acetylaminobenzthiazole is reacted in pyridine solution with p-nitrobenzenesulphonyl chloride, and the product reduced by being mixed with twice its weight of iron powder and added to very dilute boiling acetic acid, to give 2' (paminobenzenesulphonamido)-5-acetylaminobenzthiazole. (17) 2-(p-brombenzene-sulphonamido)-4-methylthiazole is treated with methyl sulphate in sodium hydroxide solution, with further additions of sodium hydroxide to give 2 - (p - brombenzenesulphonmethylamido) - 4 - methylthiazole which is then heated with concentrated ammonia in the presence of cuprous chloride to give 2 (p-aminobenzene sulphonmethylamido)-4-methylthiazole. (18) 2-amino- 5-methylthiazole is reacted in pyridine solution with p-nitrobenzenesulphonyl chloride and the product hydrolysed with caustic soda to give 2- (p-nitrobenzenesulphonamido)-5-methyl thiazole which is treated with ethyl iodide in sodium hydroxide solution to give 2-(p-nitrobenzenesulphonethylamido)-5 methyl thiazole and then reduced with iron powder and acetic acid to the corresponding p-amino compound. (19) 2-(pacetylominobenzenesulphonamido) - 4 -methylthiazole is treated with benzyl chloride in caustic soda solution to give 2-(p-acetylaminobenzenesulphonbenzylamido) -4 -methylthiazole which is hydrolysed with hydrochloric acid to the p amino body. (20) 2-(p aminobenzenesulphonamido)-4-methylthiazole is treated with dimethyl sulphate in caustic soda solution to give 2 (p-aminobenzenesulphonmethylamido)-4- methylthiazole. (21) 2-(p-acetylaminobenzenesulphonamido)-benzthiazole is treated with dimethyl sulphate in caustic soda solution to give 2-(p-acetylaminobenzenesulphonethylamido) benzthiazole which is then hydrolysed with 15 per cent. hydrochloric acid to the corresponding p-amino-compound. (22) 2-(p-aminobenzenesulphonamido) benzthiazole is treated with dimethyl sulphate in caustic soda solution to give 2:(p-aminobenzenesulphonethylamido)- benzthiazole. (23) 5-methyl-2-bromthiazole is mixed p-nitrobenzene sulphonamide, anhydrous potassium carbonate and a small amount of copper bronze and heated to 180‹ C. The melt is treated with caustic soda solution to give 5- methyl - 2 - (p nitrobenzenesulphonamido) - thiazole. This is hydrolysed with caustic soda to give 2-(aminobenzenesulphonamido)-5-methylthiazole.